If Only I Could Sleep at the Switch
Another outcome of increased stress is reduced sleep duration and impaired sleep quality, both of which are contributors to, and consequences of, obesity (see Chapter 10). BMI (body mass index) increases over time among short sleepers.37 A recent study showed that sleep deprivation increases caloric intake by 300 kcal/day, although energy expenditure was unaffected.38 You’re more likely to eat Oreos and watch infomericals about weight loss in those extra hours spent awake than you are to actually work out. Scientists are constantly conducting research to better understand the different parts of the brain. You’ve likely seen at least one horror or action movie in which a person is strapped to a bed with an electrical helmet, being monitored by men in white lab coats. In real life these types of studies are well monitored for safety and are incredibly valuable in understanding how we tick. When healthy people were asked to spend the night in a lab and deprived of sleep, their brain imaging showed less activation in the PFC but greater activation in the amygdala when choosing foods. Do you think they went for the carrots or the cookies?39 On nights back in pediatric residency (post-doctoral training where you ostensibly sleep in the hospital), mint Milanos were my only true and unflagging companion that I could always rely on. Poor sleep is common among obese individuals. They often suffer from obstructive sleep apnea (see Chapter 18). They retain more carbon dioxide, which makes them even hungrier, and makes their obesity and diabetes even worse and puts an extra strain on their heart.40 So stress leads to sleep deprivation. Sleep deprivation causes more reactivity and cortisol release. Cortisol release alters your dopamine response curve. Increased dopamine makes you more likely to eat. The more you eat, the more likely you are to become obese. Obesity leads to sleep deprivation, which can cause stress. A truly vicious cycle.
The Vulnerable Child
Stress and cortisol play an even bigger role in children, a time when eating patterns are programmed.41 Adverse childhood experiences and early life stressors, such as child abuse, dramatically change the brain,42 and these changes predispose children to adult obesity and related disorders.43 Several studies have shown relationships between stress and unhealthy dietary practices, including increased snacking in adolescents.44 In a study of nine-year-olds, children who felt more stressed by lab challenges ended up eating more comfort food.45 Not only are stressed kids setups for obesity, they’re setups for future abuse of other substances as well.46
When you’re under stress, your cortisol is up, your PFC is inhibited, your dopamine is firing—all of which will drive you to the chocolate cake or another drug of choice. The more chocolate cake you eat in response to stress, the less pleasure you will get and the sicker you will start to feel, which will drive even more stress. Those dopamine receptors need more, but deliver less. You’ll soon become tolerant or, worse yet, addicted.
5.
The Descent into Hades
There’s a price to pay for reward. It used to be measured in dollars, pounds, or yen, but now it’s measured in neurons. As the monetary price of reward fell, the physiological price of reward skyrocketed. Because those dopamine receptor–harboring nucleus accumbens (NA) neurons are fragile. They want to be tickled; that’s why they have dopamine receptors in the first place. But they’re very sensitive; they don’t want to be bludgeoned. If you open the dopamine floodgates repeatedly, these neurons have some fail-safe methods built in to protect themselves.
The goal is to have an optimal level of dopamine receptors so that even a minuscule dopamine rush (trip to the nail salon) can find an open receptor and generate a unique pleasure from the experience. Obviously, a bigger rush (a couple of glasses of scotch or jumping out of an airplane) will occupy more receptors and generate a bigger reward. But stimulating the dopamine receptors excites that next neuron in the NA, and overstimulation with multiple rapid firings can cause those receptor-containing neurons to go into overdrive, leading to cell damage or death, termed excitotoxicity. To protect themselves from your irrational exuberance, each neuron has a built-in subcellular program that reduces the number of receptors on its surface. The more dopamine chronically released from the VTA neuron, the fewer dopamine receptors will be available on the NA neuron to transduce the signal for reward. This is the law of mass action—everything kept in check.
The Firing Squad
When cells in your body die, they are usually replaced with new ones. Not so with the brain, with few exceptions (like the hippocampus, which plays a role in the depression story). Once a primitive brain cell (neuroblast) turns into a functioning neuron and starts firing, it loses the capacity to divide again.1 Clearly, chronic stimulation of neurons, resulting in cell death with no chance for replacement, is not in your best interest. So nature developed a plan B that is semi-protective. Ligands (molecules that bind to receptors, such as dopamine or cortisol) almost uniformly down-regulate their own receptors, all over the body. In other words, nature makes it so that the locks can be rekeyed or even shut down. But it also means that the response of the cell won’t be as robust the next time around. You will need more to get less.
The down-regulation of receptors is a phenomenon called tolerance; the receiving neuron is becoming tolerant to the excessive stimulus. This is both good and bad. It’s good because it means your neurons aren’t dead. It’s bad because the next time you go looking, you’re going to need more of the substance in order to get the same level of reward. Which ups the ante. Tolerance is a standard response in medicine, and occurs with virtually every chemical that binds to a receptor, whether it be in the brain, the gut, the muscle, the liver, or anywhere else for that matter. Tolerance is how cells, and you, survive.
But when neurotransmitters bludgeon the receiving neuron en masse and without cessation, they can overstimulate and eventually kill that neuron through a process of programmed cell death called apoptosis. Chronic excitation of almost any neuron can lead to cell death. This is a common phenomenon in neuroscience, and it’s a necessary process. Apoptosis is inherent to all cells in the body; it’s the self-destruct program that keeps good cells from turning bad (e.g., cancer).
Trimming and Pruning
There are two ways for a cell to die: necrosis (poisoning it from the outside) or apoptosis (self-destruction from the inside). Drugs can do both: they can poison the cell outright, or they can beat it into permanent submission. Apoptosis is a normal and very important process throughout the body that clears away overworked, mutated, or just plain old and decrepit cells. It is especially important during gestation in the womb. We all start out as a single cell—a zygote—and by adulthood we end up as a conglomeration of 10 trillion cells, which have differentiated into hundreds of various cell types along the way. Think of apoptosis as the human equivalent of bonsai, the Japanese art of pruning and sculpting trees to take on new and beautiful dimensions; otherwise they’re just gangly weeds. And throughout the various organs of the body—except for the majority of the brain—we maintain the capacity to be able to divide, regrow, and replace cells even as they are cleared away by apoptosis.
Adults appear smarter than toddlers for three reasons: they have more white matter (the fatty part of the brain that insulates neurons and helps transmit impulses faster), which increases information transmission speed; they have a more developed PFC (the executive function center, or Jiminy Cricket, of the brain); and they generally have more experience to draw on. But the number of neurons remains the same. That’s why IQ tests can be administered as early as age four. If your four-year-old self could see you now, Marlon Brando’s words from On the Waterfront (1954) would no doubt reverberate: “I coulda been somebody. Instead of a bum, which is what I am.” So keeping your neurons happy and healthy throughout your life should be part of your prime directive.
Yet many of us spend our lives bombarding our synapses with substances and behaviors that down-regulate receptors through the law of mass action (see Chapter 3) or that act as poison
s (e.g., alcohol), taking out perfectly good neurons, or with substances that provide different forms of excitation, including illicit drugs of abuse,2 or too much coffee, too much stress, and not enough sleep.3 They either rapidly necrose from the outside or, more likely, slowly apoptose from the inside. And then pleasure is strewn to the wind, because those neurons are not coming back. This process is different from developing tolerance. Tolerance is the down-regulation of receptors with the chance of coming back. Once a neuron is dead, it ain’t never coming back. There’s less to work with, and you can’t make more neurons. All of which comes down to the same result: you need more to get less.
As an illustration, let’s choose a peanut butter cup, the cheapest of all thrills (but it just as easily could be a shot of espresso or vodka). In terms of the reward neuron, the initial script’s the same: Get a desire (dopamine). Get a fix. Get a temporary rush (EOPs). Yum. But, man, that peanut butter cup was so delicious. Just the right amount of peanut butter, salt, chocolate, and sugar. Specifically engineered to hit your bliss point as chronicled by Michael Moss.4 Go ahead, eat the second one—they come two to a package, after all. Get another rush; this one won’t last as long as the first one because there are fewer receptors. Tomorrow, you go get another package at Walgreens—they’re staring at you right on the counter—and dig in for your third hit, but you just can’t recapitulate that gustatory nirvana again. More should be able to do it: the next day, you buy the six-pack. And now that extra fix means your receptors are down-regulated even more. So you decide to put the pedal to the metal: the economy-size bag has now become your standard, and it’s just giving you way less response than you ever had. The cashier at Safeway now recognizes you. And now you have so few reward-transducing receptors, you hardly break a smile. You want the yum, but even after eating the Halloween-size bag and a couple of pints of ice cream while watching The Notebook (2004), you still aren’t satisfied.
Pickling Your Brain
Every substance and behavior that drives up your reward triggers will just as quickly drive down your reward receptors. Different types of rewards, chronically and in excess, all have the same effect. Why is it that alcoholics can consume so much more booze than your average drinker? Their livers have a much higher tolerance, because repeated and high exposure has increased their capacity to metabolize the alcohol. Their brains also have a higher tolerance because the alcohol has been driving those VTA neurons, which have been bombarding those receptors in the NA with dopamine for so long, they need a lot more to fly the friendly skies. A true lush will get less pleasure from a pint of bourbon than your average normal drinker would get from a single cocktail.
If you stop the nosedive here before your neurons are deep-sixed, you have a fighting chance of pulling out, like a withered flower that’s waiting for rain. If the postsynaptic neurons are only damaged but still alive, your dopamine receptors can regenerate over time.5 You can bring your reward system back and start over, although dopamine receptors aren’t back to normal for at least twelve months.6 One reason for overdose is that addicts, after coming out of a period of abstinence stemming from rehab or jail, will go straight for the last dosage of their drug of choice. Because they no longer have the same level of tolerance, their previous dose is now an overdose.
But keep nosediving and you’re sure to crash. Next on the hit parade is the snowball effect. Your VTA dopamine neurons, the drivers of the reward signal, are themselves in overdrive. They’re working their little nuclei off trying to manufacture more enzymes to make more dopamine (even though your pleasure quotient is almost negligible because those dopamine receptors are so down-regulated). Now both your dopamine neurons and their target receptors are flirting with initiating that apoptotic self-destruct sequence. At some point down the line, they’re going to give up. You now have much less of the reward pathway than you used to. You’ll never reach the same level of reward as before—ever—because you just don’t have the machinery to do so. You’re constantly trying to recapture that first high, “chasing the dragon,” but you’ll never be able to because those neurons are dead. When you fly with one engine, you’re much more apt to crash and burn. People in recovery from illicit substances have a motto: “Once a cucumber becomes a pickle, it will never be a cucumber again.”
But wait, there’s more! A third phenomenon often comes part and parcel with tolerance. Some of our favorite rewards have extra pain built right in. Once you’ve become tolerant, and you’re spending your salary to maintain your fix, you wake up and decide it’s time to quit. But changes in those neurons have occurred. The acute cessation of many of these substances can lead to severe and extremely unpleasant experiences, known as withdrawal. They tend to cluster as symptoms of physiological withdrawal (e.g., caffeine, alcohol, narcotics, and tranquilizers) with effects on the body, such as sweating, racing heart, palpitations, muscle tension, chest tightness, difficulty breathing, tremor, and GI complaints such as nausea, vomiting, and diarrhea. Some, like delirium tremens (DTs) from alcohol withdrawal, or hallucinations from benzodiazepine (benzos) or barbiturate (downers) withdrawal, can be life-threatening. Or symptoms can cluster as manifestations of emotional withdrawal (e.g., from cocaine, marijuana, and ecstasy), with effects on the brain such as anxiety, restlessness, irritability, insomnia, headaches, poor concentration, depression, and social isolation.7 These symptoms of withdrawal can be so severe as to prevent people from even wanting to give up their drug/behavior of choice, and they often lead abusers to relapse. Tolerance and withdrawal are the classic two-headed hydra of the definition of addiction.
An Equal Opportunity Offender
When there is too much dopamine, there can be too much motivation to obtain your pleasure. The motivation—the wanting—becomes more of a needing. Many addicts commit a host of crimes to obtain their fix, often hurting loved ones in the process. They drive drunk, lose custody of their children, and not infrequently become destitute. It can happen to anyone. A friend of mine recently had back surgery and was prescribed oxycodone (OxyContin). Within a brief time period, she stopped needing the drug to ameliorate her physical pain, but she still needed it to occupy those few remaining opioid receptors. She became a drug-seeking doctor shopper, doing whatever she could to fill her next prescription. The pain she suffered was not from her back but rather from the desperation to obtain her next fix. Her dopamine put her in 24/7 motivation overdrive, while her oxycodone didn’t pack the punch she needed to calm herself down. We often hear of famous people entering the Betty Ford Center to dry out. Did they get addicted and then get famous? No, drug abuse is a response to the stresses of everyday life. And apparently famous people have stresses too.
People often say addiction is a choice—after all, Nancy Reagan argued that you could “just say no.” And despite overwhelming evidence that nicotine caused both tolerance and withdrawal, the tobacco industry used “free choice” as its cornerstone defense from the 1960s through the 1990s. In 1994, on national television, Thomas Sandefur (CEO of Brown & Williamson), William Campbell (CEO of Philip Morris), and James Johnston (CEO of R.J. Reynolds) all testified under oath “I believe that nicotine is not addictive.”8 So how did the tobacco companies get away with saying nicotine was not addictive, and for so long? What were the criteria? Well, they couldn’t deny tolerance and withdrawal, so they played down the concern by equating it with other hedonic substances. According to the tobacco companies, “Addiction is an emotive subject and it is certainly possible to define the term broadly enough to include smoking . . . the current definition is more colloquial . . . and certainly applies to the use of many common substances that have familiar pharmacological effects to cigarettes, such as coffee, tea, chocolate and cola drinks.”9 Hey, don’t pick on us, we’re no worse than Coca-Cola!
Whether they knew it or not, they actually got it right. Individuals in society have found pleasure in all forms of reward—to each his own. Some of those are substances. And some are behaviors, which we e
ngage in specifically because they feel good. It doesn’t matter: the final common pathway is dopamine. Some behaviors are innate, like eating and sex. Some are learned, like shopping or shoplifting or gambling or gaming or texting or bingeing on Netflix (see Chapter 14). Similar to taking drugs of abuse, overperforming each of these behaviors can also manifest the phenomenon of tolerance (i.e., performing the behavior more and more to get less and less reward). Some will be so driven by their dopamine to greater and greater extremes to get that ever-diminishing EOP rush that they will escalate up to deviant behavior, some of which are severe enough to put you face-to-face either with the law or with your maker.
How are these behaviors, as bizarre as they are, considered addictions? While they clearly manifest tolerance (more and more for less and less), they do not demonstrate either the physiological or emotional consequences of withdrawal upon cessation.10 Tolerance without withdrawal—is that addiction? The American Psychiatric Association (APA), the professional society of psychiatrists, are the gurus in this field. They are the publishers of the definitive Diagnostic and Statistical Manual (DSM), which defines and categorizes all psychiatric and behavioral disorders.11
The Hacking of the American Mind Page 7